A VicRK Signal Transduction System in <i>Streptococcus mutans</i> Affects <i>gtfBCD</i> , <i>gbpB</i> , and <i>ftf</i> Expression, Biofilm Formation, and Genetic Competence Development

<jats:title>ABSTRACT</jats:title> <jats:p> Bacteria exposed to transient host environments can elicit adaptive responses by triggering the differential expression of genes via two-component signal transduction systems. This study describes the <jats:italic>vicRK</jats:italic> signal transduction system in <jats:italic>Streptococcus mutans</jats:italic> . A <jats:italic>vicK</jats:italic> (putative histidine kinase) deletion mutant (SmuvicK) was isolated. However, a <jats:italic>vicR</jats:italic> (putative response regulator) null mutation was apparently lethal, since the only transformants isolated after attempted mutagenesis overexpressed all three genes in the <jats:italic>vicRKX</jats:italic> operon (Smuvic <jats:sup>+</jats:sup> ). Compared with the wild-type UA159 strain, both mutants formed aberrant biofilms. Moreover, the <jats:italic>vicK</jats:italic> mutant biofilm formed in sucrose-supplemented medium was easily detachable relative to that of the parent. The rate of total dextran formation by this mutant was remarkably reduced compared to the wild type, whereas it was increased in Smuvic <jats:sup>+</jats:sup> . Based on real-time PCR, Smuvic <jats:sup>+</jats:sup> showed increased <jats:italic>gtfBCD</jats:italic> , <jats:italic>gbpB</jats:italic> , and <jats:italic>ftf</jats:italic> expression, while a recombinant VicR fusion protein was shown to bind the promoter regions of the <jats:italic>gtfB</jats:italic> , <jats:italic>gtfC</jats:italic> , and <jats:italic>ftf</jats:italic> genes. Also, transformation efficiency in the presence or absence of the <jats:italic>S. mutans</jats:italic> competence-stimulating peptide was altered for the <jats:italic>vic</jats:italic> mutants. In vivo studies conducted using SmuvicK in a specific-pathogen-free rat model resulted in significantly increased smooth-surface dental plaque (Pearson-Filon statistic [PF], <0.001). While the absence of <jats:italic>vicK</jats:italic> did not alter the incidence of caries, a significant reduction in SmuvicK CFU counts was observed in plaque samples relative to that of the parent (PF, <0.001). Taken together, these findings support involvement of the <jats:italic>vicRK</jats:italic> signal transduction system in regulating several important physiological processes in <jats:italic>S. mutans</jats:italic> . </jats:p>